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In-Depth Information
7
Communication Using
Engineered Genetic
Regulatory Networks
Ron Weiss, Thomas F. Knight Jr.,
and Gerald Sussman
In this chapter we demonstrate the feasibility of digital computation in cells by
building several operational
in vivo
digital logic circuits, each composed of three
gates that have been optimized by genetic process engineering. We have built
and characterized an initial cellular gate library with biochemical gates that im-
plement the NOT, IMPLIES, and AND logic functions in
E. coli
cells. The logic
gates perform computation using DNA-binding proteins, small molecules that
interact with these proteins, and segments of DNA that regulate the expression
of the proteins. We also demonstrate engineered intercellular communications
with programmed enzymatic activity and chemical diffusions to carry messages,
using DNA from the
Vibrio fischeri lux
operon. The programmed communica-
tions is essential for obtaining coordinated behavior from cell aggregates.
This chapter is structured as follows: the first section describes experimental
measurements of the device physics of
in vivo
logic gates, as well as genetic
process engineering to modify gates until they have the desired behavior. The
second section presents experimental results of programmed intercellular com-
munications, including time-response measurements and sensitivity to varia-
tions in message concentrations.
MEASURING AND MODIFYING DEVICE PHYSICS
Potentially the most important element of biocircuit design is matching gate
characteristics. Experimental results in this section demonstrate that circuits
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